Harrington, NE, Kottara, A, Cagney, K, Shepherd, MJ, Grimsey, EM, Fu, T, Hull, RC, Childs, DZ, Fothergill, JL, Chalmers, JD et al (show 2 more authors)
(2024)
Global genomic diversity of<i>Pseudomonas aeruginosa</i>in bronchiectasis.
[Preprint]
Abstract
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p><jats:italic>Pseudomonas aeruginosa</jats:italic>is the dominant pathogen causing lung infections in people with both cystic fibrosis (CF) and bronchiectasis, associated with poorer outcomes. Unlike CF, bronchiectasis has been a neglected disease. More extensive genomic studies of larger bronchiectasis patient cohorts and within patient sampling are needed to improve understanding of the evolutionary mechanisms underpinning<jats:italic>P. aeruginosa</jats:italic>infections to guide novel and improved treatments.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We have performed genome sequencing of 2,854<jats:italic>P. aeruginosa</jats:italic>isolates from 180 patients attending clinics worldwide to analyse the genomic diversity between and within patient infections.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We observed high genetic diversity between infections with low incidence of highly transmissible strains. Our genomic data provide evidence for the mutational targets driving<jats:italic>P. aeruginosa</jats:italic>evolution in bronchiectasis. Some functions found to gain mutations were comparable to CF, including biofilm and iron acquisition, whilst others highlighted distinct evolutionary paths in bronchiectasis such as pyocin production and resistance, and a novel efflux pump gene (PA1874). We also show a high incidence of antimicrobial resistance-associated mutations and acquired resistance genes, in particular multidrug efflux and fluoroquinolone resistance mechanisms.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our findings highlight important differences between<jats:italic>P. aeruginosa</jats:italic>infections in bronchiectasis and CF and provide evidence of the relatively minor role transmissible strains play in bronchiectasis. Our study provides a 10-fold increase in the available genomic data for these infections and is a global resource to improve our knowledge and understanding, to facilitate better patient outcomes.</jats:p></jats:sec><jats:sec><jats:title>Summary</jats:title><jats:p>The largest genomic study of<jats:italic>Pseudomonas aeruginosa</jats:italic>bronchiectasis isolates to-date, providing an unprecedented global genomic resource. We highlight important differences between bronchiectasis and cystic fibrosis, including key genes under selection.</jats:p></jats:sec>
| Item Type: | Preprint |
|---|---|
| Uncontrolled Keywords: | Lung, Biotechnology, Cystic Fibrosis, Rare Diseases, Infectious Diseases, Human Genome, Clinical Research, Antimicrobial Resistance, Genetics, 2.1 Biological and endogenous factors, 2 Aetiology, 2.2 Factors relating to the physical environment, Congenital, Infection, 3 Good Health and Well Being |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 13 Feb 2024 09:11 |
| Last Modified: | 15 Mar 2024 03:43 |
| DOI: | 10.1101/2024.01.30.577916 |
| Open Access URL: | https://www.biorxiv.org/content/10.1101/2024.01.30... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178619 |
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